Progression-free and overall survival in patients with relapsed/refractory germ cell tumors treated with single-agent chemotherapy: Endpoints for clinical trial design

Authors

  • Darren R. Feldman MD,

    Corresponding author
    1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Medical College of Cornell University, New York, New York
    • Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065

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    • Fax: (212) 988-0701

  • Sujata Patil PhD,

    1. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Michael J. Trinos BS,

    1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Maryann Carousso NP,

    1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Michelle S. Ginsberg MD,

    1. Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Joel Sheinfeld MD,

    1. Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York
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  • Dean F. Bajorin MD,

    1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Medical College of Cornell University, New York, New York
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  • George J. Bosl MD,

    1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Medical College of Cornell University, New York, New York
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  • Robert J. Motzer MD

    1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
    2. Weill Medical College of Cornell University, New York, New York
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  • The results of this study were presented in part at the 45th Annual Meeting of the American Society of Clinical Oncology, June 7, 2010; Orlando, FL.

Abstract

BACKGROUND:

Refractory germ cell tumor (GCT) patients have a poor prognosis and limited treatment options. The identification of novel active agents may be impaired by use of response as the primary endpoint in phase 2 trials. Improved endpoints could enhance the development of new effective agents.

METHODS:

The characteristics and outcome of refractory GCT patients enrolled in 7 single-agent phase 2 trials conducted at Memorial Sloan-Kettering Cancer Center from 1990 to 2008 were reviewed. The study agents were suramin, all-transretinoic acid, topotecan, pyrazoloacridine, temozolomide, ixabepilone, and sunitinib. The major endpoints evaluated were response, progression-free survival (PFS), and overall survival (OS).

RESULTS:

Ninety patients (87 male, 3 female) were treated. The primary tumor site was testis in 65 patients, mediastinum in 17 patients, retroperitoneum in 4 patients, and other in 4 patients. Eighty-six patients had nonseminoma, and 4 patients had pure seminoma. Best responses were 1 (1%) partial response (ixabepilone), 15 (17%) stable disease, and 74 (82%) progressive disease. Median PFS and OS were 1.0 month (95% confidence interval [CI], 0.8-1.3) and 4.7 months (95% CI, 3.5-6.4), respectively. Eighty-six of the 90 patients have died. The 12- and 16-week PFS rates were 9% (95% CI, 3-15%) and 6% (95% CI, 1%-11%), respectively.

CONCLUSIONS:

Patients with refractory GCT progressed rapidly to these single agents. PFS and OS may be useful endpoints for designing phase 2 trials testing novel agents in this population. Twelve-week PFS (with comparison to the 9% benchmark rate reported herein) is the recommended endpoint for phase 2 trial design and median OS (using 4.7 months as the predicted median for the control arm) is suggested for phase 3 trials. Cancer 2012;. © 2011 American Cancer Society.

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